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Systolic and Diastolic BP Control in Metabolic Syndrome Patients with Metadichol® a Novel Nano Emulsion Lipid

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Metadichol® a nano formulation and mixture of long chain alcohols that is present in many foods like rice and sugar cane. It is derived from the waste of the sugar cane industry and therefore, it is a renewable resource. Most of the clinical data in the literature are from non-nano formulations either in a tablet or a capsule form which has not shown any efficacy. Given its safety profile, we carried out a small open label pilot study on 14 diabetic patients with hypertension. These patients had co-morbidities such as dyslipidemia, obesity and hypertension, but were not on any hypertensive medication. In this open label study, we treated the patients with 20mg of Metadichol per day for 60 weeks. The results showed that it is possible to bring about improvements in Systolic and Diastolic blood pressure in addition to CRP, VLDL, HDL, Triglycerides, waist circumference reduction, and reduction in insulin resistance. Interestingly, the average Vitamin C level for this study group also doubled. This study showed a vast improvement over existing therapies and with no reported side effects (minor or major).
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Case Report
Volume 5 Issue 2 - May 2017
DOI: 10.19080/JOCCT.2017.05.555660
J Cardiol & Cardiovasc Ther
Copyright © All rights are reserved by PR Raghavan
Systolic and Diastolic BP Control in Metabolic
Syndrome Patients with Metadichol® a Novel Nano
Emulsion Lipid
PR Raghavan*
Nanorx Inc., USA
Submission: April 10, 2017; Published: May10, 2017
*Corresponding author: PR Raghavan, Nanorx Inc., PO Box 131, Chappaqua, NY 10514, USA, Email:
Introduction
It is paradoxical that despite the enormous advances in
antihypertensive drug therapy, the Number of people with
uncontrolled hypertension has continued to rise. A new 2017
study [2] by the American Heart Association, projects that
by 2035, cardiovascular disease (CVD), will become the most
expensive and prevalent killer if left unchecked, will place a
   
and health care systems. According to the study, in the next
two decades, the number of Americans with CVD will rise to
131.2 million-45 percent of the total U.S. population with costs
expected to reach $1.1 trillion. There are many hypertensive
drugs, but prolonged use and multi-drug use does lead over time
to side effects. There is a need for a safe, cheap alternative to
existing drugs. Metadichol is a Nanoemulsion of long-chain lipid
alcohols (C-26, C-28, and C-30), which are commonly known as
Policosanols. and it binds to VDR and which has been shown to
have a role in hypertension [1,3-5].
Open label study
Fourteen patients were enrolled in Nonrandomized, Open,
        
Metadichol in subjects with metabolic syndrome at a hospital
in Bangalore, India. The dosage was 20mg per day. Most of
the patients were on antidiabetic medication Metformin
and Glucophage in addition. None of the patients were on
hypertensive medication.
Diagnosis and main criteria for inclusion
The study population consisted of male or non-pregnant
female patients aged 18 years of age with a previously diagnosed
various medical conditions. All patients provided written
informed consent to participate in the study before being
screened.
The patient information sheet detailed the procedures
involved in the survey (aims, methodology, potential risks,
J Cardiol & Cardiovasc Ther 5(2): JOCCT.MS.ID.555660 (2017) 001
Abstract
Metadichol®, [1] a nano formulation a mixture of long chain alcohols that is present in many foods like rice and sugar cane and is derived
from the waste of the sugar cane industry. It is a renewable resource. Most of the clinical data in literature is a: non-nano formulation either a

                    
morbidities such as dyslipidemia, obesity, and hypertension. None of them were on any hypertensive medication.
Our studies on patients for 60 weeks in an open-label study @20mg per day showed that it is possible to bring about improvements in
Systolic and diastolic pressure in addition to CRP, VLDL, HDL, Triglycerides and waist circumference reduction and reduction in insulin resistance.
Interestingly Vitamin C levels doubled. The study showed a vast improvement over existing therapies and with no side effects minor or major
to report.
Keywords: Metadichol; VDR; Inverse agonist; Protean agonist; CVD; Systolic diastolic; CRP; HDL; LDL; Albumin; Globulin; Vitamin C; Gulo;
Policosanol; TNF alpha; PAI-1; MCP-1
Journal of Cardiology & Cardiovascular erapy
How to cite this article: P.R. Raghavan. Systolic and Diastolic BP Control in Metabolic Syndrome Patients with Metadichol® a Novel Nano Emulsion Lipid.
J Cardiol & Cardiovasc Ther 2017; 5(2): 555660. DOI: 10.19080/JOCCT.2017.05.555660.
002

patient. The patient signed the consent form to indicate that the
information had been disclosed and understood. The patient was
then allowed time to consider the information presented before
signing and dating the informed consent form to indicate that
they fully understood the information, and willingly volunteered
to participate in the study. The patient was given a copy of the
informed consent form for their information. The original copy
           
Investigators center records.
Criteria for exclusion from the study included pregnant
or lactating females any serious and uncontrolled medical
conditions interfering with the study or placing the patient at
        
criteria and did not meet any of the exclusion criteria were
enrolled into the study.
Safety Results
       
incidences of adverse events and good compliance. Vital signs
were all within the normal range during the study. There were
         
in the treatment groups. Physical examination was found to
be normal during the study for all the subjects. There were no

Analysis of Variance one way was carried out using JMP
software from SAS showed that the following biomarkers were

a) Systolic and diastolic pressure
b) hS-CRP (high sensitivity C-reactive protein)
c) Experimental VLDL
d) Vitamin C
e) A/G ratio and Globulins
f) Triglyceride/HDL ratios
g) e-GFR a biomarker of kidney function.
Discussion of Results
The key biomarkers that are the subject of this
communication are Systolic, diastolic CRP, VLDL as well as A/G
ratios and Globulin. Table 1, Figures 1 & 2 and Table 2& 3 show
changes with descriptive statistics for Systolic and diastolic
pressures. The most striking result was the normalization of
blood pressure in 3 weeks.
Table 1:
Biomarker Change (%) p value units
Systolic Pressure -20.13 0.0002 mm Hg
Diastolic Pressure -14.2 0.01 mm Hg
VLDL -58.7 0.00065 mg/dl
Triglyceride ratio
(mmol/mmol) -34 0.04 mg/dl
hs-CRP -47.2 0.045 mg/dl
Vitamin C 100 0.00062 mg/dl
A/G ratio -285 0.00 number
Globulin -22.9 0.0029 g/dl
eGFR 42.5 0.0356 ml/min/1.73
M2
HDL 15.4 0.14 mg/dl
Fasting Sugar -10 -- MG/DL
Insulin Resistance -12.5 -number
Figure 1: Average systolic pressure.
Figure 2: Average diastolic pressure.
Journal of Cardiology & Cardiovascular erapy
How to cite this article: P.R. Raghavan. Systolic and Diastolic BP Control in Metabolic Syndrome Patients with Metadichol® a Novel Nano Emulsion Lipid.
J Cardiol & Cardiovasc Ther 2017; 5(2): 555660. DOI: 10.19080/JOCCT.2017.05.555660.
003
Table 2: Average systolic pressure.
Analysis of Variance (One-Way)
Descriptive Statistics
Groups Sample size Sum Mean Variance
A14.00 2,096 149.71 320,120
B14.00 1,760 125.71 223,600
C14.00 1,700 121.43 208,000
D14.00 1,695 121.07 207,125
E14.00 1,690 120.71 205,500
F14.00 1,670 119.29 201,900
Total 84.00 126.32 311.43
ANOVA
Source of
Variation d.f. SS MS Fp-value F crit Omega Sqr.
Between
Groups 5.00 9,520.5 1,904.1 9.10 0.00 2.33 0.33
Within Groups 78.00 16,327.8 209.3
Total 83.00 25,848.3
Table 3: Average diastolic pressure.
Analysis of Variance (One-Way)
Descriptive Statistics
Groups Sample size Sum Mean Variance
A14 1,223 87.36 109,083
B14 1,150 82.14 95,100
C14 1,116 79.71 90,296
D14 1,070 76.43 82,700
E14 1,080 77.14 83,800
F14 1,050 75.00 79,700
Total 84 79.63 96.71758
ANOVA
Source of
Variation d.f. SS MS Fp-value F crit Omega Sqr.
Between
Groups 51,454.63 290.926 3.45238 0.00718 2.332 0.127
Within Groups 78 6,572.93 84.268
Total 83 8,027.560
Nesri et al. [6] found that weekly vitamin D supplementation

of blood pressure in type 2 diabetic patients. Another recent
study [7] also showed a use of 2000 IU Vitamin D showed the
drop of 10mm Systolic and 6mm diastolic. Given that Metadichol
binds to Vitamin D the results are not surprising. The effects go
beyond that. Even more remarkable is its effects on lipids VLDL
    
levels. Lieffard et al. [8] showed that higher levels of Vitamin D
are associated with lower levels of C-reactive protein.
Metadichol binds to the vitamin D receptor (VDR) as an
inverse agonist. It is the only known inverse agonist of VDR
known today. Calcitriol (1,25-Dihydroxy Vitamin D) is the
natural ligand for the VDR and acts as an agonist. Metadichol acts
an inverse agonist but more likely is a Protean agonist. Protean
agonists act as both positive and negative agonists on the same
receptor depending on the degree of constitutive activity that
is present. If there is no constitutive activity, the agonist would
be an active agonist. When constitutive activity is present, the
Protean agonist would be an inverse agonist [9]. In addition
to VDR binding, Metadichol shares cross-reactivity with other
nuclear receptors, like PPAR gamma [10], which may explain its
activity against a broad range of biomarkers.
Even more striking is that Vitamin C levels doubled. It is
well known that our ancestors had a functioning gene GULO
that converted glucose into Vitamin C [11]. Humans once made
Journal of Cardiology & Cardiovascular erapy
How to cite this article: P.R. Raghavan. Systolic and Diastolic BP Control in Metabolic Syndrome Patients with Metadichol® a Novel Nano Emulsion Lipid.
J Cardiol & Cardiovasc Ther 2017; 5(2): 555660. DOI: 10.19080/JOCCT.2017.05.555660.
004
vitamin C in their liver by the production of four enzymes
which convert circulating sugars into ascorbic acid (vitamin
C). Humans today only make 3 of the four enzymes required
to convert glucose (sugar) into Ascorbic acid. A progressive
mutation at some time in past generations deactivated the
gene for the enzyme gluconolactone oxidase and slowly as the
mutation progressed the synthesis of vitamin C came to an end
          
exogenous sources today. This has led to inactivity of the enzyme
L-gulonolactone [12].
Mammals who make their vitamin C can live 8-10 times
beyond their age of physical maturity. Mammals without this
        
believe the reinstallation of the guano-lactone oxidase enzyme
in humans would extend the lifespan of humans [13,14].
A study over a 12-16-year period showed that males with
the highest blood serum levels of vitamin C experienced a 57
percent drop in their risk of dying from any cause compared to
males with low circulating levels of vitamin C [15]. Among men
and women ages 45-79 years, just a 50 milligram increase in
vitamin C consumption was enough to reduce the relative all-
cause mortality rate by 20 percent [16].
        
percent decreased all-cause mortality rate among adults with
normal to high circulating levels of vitamin C [17].
Since vitamin C is an antioxidant and reduces C-reactive
protein (CRP)-a substance that can support the progression of
CVD [18]. In fact, in a study of active and passive smokers, vitamin
C supplementation (515mg daily) resulted in a 24-percent
reduction in plasma CRP. Ascorbate stimulates the immune
system and can help those with impaired immunity [19,20]. Low
      
very low density lipoproteins [21].
Today’s approach in drug research is a lock and key, with a

drug target. Given the many side effects of drugs and to overcome
it the search for high selective ligands has been the approach
of the drug discovery community. This has not delivered any
        
multiple proteins rather than single targets. Anti-psychotic
drugs commonly exhibit a broad spectrum of activities across
entire families of serotonin and dopamine receptors. Protein
kinase inhibitors like Sutent and Gleevec, have demonstrated
that their anticancer effects are most likely due to their action
on multiple signaling kinases [22].
         
each lock is more common than one key to open many locks.
Their hypothesis based on available data of drug action using
network biology provided insights into how we can improve
drug discovery for complex diseases. Medicines for many disease

with the observation that perturbed biological networks is more
important than individual targets. Such an approach has been
highlighted and advocated by Andrew Hopkins [24].
Effective drugs act via modulation of multiple proteins
rather than single targets. Metadichol does just that. It seems to
be operate by optimizing multiple activities, and balancing drug-
like properties and eliminating undesirable off target effects.
The inverse/protean activity exhibited by Metadichol leads to it
acting on more than one target, VDR, PPAR gamma as well as
inhibition of cytokines like TNF-alpha, MCP-1, PAI-1 and also the
endogenous increase of Vitamin C levels which we have shown
in our Rat studies [1]. Given the range and breadth of actions of
Metadichol the results suggest that it mimics the effects of 1,25,
dihydroxy Vitamin D3 but without the toxic effect secondary to
calcemia which limits its use as a pharmaceutical agent [25].
          
simultaneously modulate multiple targets which could pave
the way to successful treatment of many of these challenging
diseases [26-31].
Conclusion
The results of this study demonstrate that Metadichol
          
the Improvement of the levels Various biomarkers especially
Systolic and diatonic blood pressure and markers of CVD like
CRP and VLDL. It has the potential to be an effective approach in
overcoming hypertension and markers related to CVD diabetes
and lipid disorders. Metadichol has a particle size of less than
60nm and has the potential to serve as an anti-hypertensive and
       
particularly given that its constituents (long-chain lipid alcohols)
are present in foods commonly daily and has shown any toxicity
even at doses of up to 5000mg/kg [31-33]. Metadichol could
be used as a preventive nutritional supplement as a cheaper
and a far effective substitute to prescription drugs, which have
been largely ineffective in hypertension and many other chronic
diseases and have many side effects that add to health care costs.
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DOI: 10.19080/JOCCT.2017.05.555660
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Background: Cross-sectional studies have found an association between deficiencies in serum vitamin D, as measured by 25-hydroxyvitamin D (25[OH]D), and an atherogenic lipid profile. These studies have focused on a limited panel of lipid values including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Objective: Our study examines the relationship between serum 25(OH)D and an extended lipid panel (Vertical Auto Profile) while controlling for age, gender, glycemic status, and kidney function. Methods: We used the Very Large Database of Lipids, which includes US adults clinically referred for analysis of their lipid profile from 2009 to 2011. Our study focused on 20,360 subjects who had data for lipids, 25(OH)D, age, gender, hemoglobin A1c, insulin, creatinine, and blood urea nitrogen. Subjects were split into groups based on serum 25(OH)D: deficient (<20 ng/mL), intermediate (≥ 20-30 ng/mL), and optimal (≥ 30 ng/mL). The deficient group was compared to the optimal group using multivariable linear regression. Results: In multivariable-adjusted linear regression, deficient serum 25(OH)D was associated with significantly lower serum HDL-C (-5.1%) and higher total cholesterol (+9.4%), non-HDL-C (+15.4%), directly measured LDL-C (+13.5%), intermediate-density lipoprotein cholesterol (+23.7%), very low-density lipoprotein cholesterol (+19.0%), remnant lipoprotein cholesterol (+18.4%), and TG (+26.4%) when compared with the optimal group. Conclusion: Deficient serum 25(OH)D is associated with significantly lower HDL-C and higher directly measured LDL-C, intermediate-density lipoprotein cholesterol, very low-density lipoproteins cholesterol, remnant lipoprotein cholesterol, and TG. Future trials examining vitamin D supplementation and cardiovascular disease risk should consider using changes in an extended lipid panel as an additional outcome measurement.
Article
Background: Vitamin D is an important mediator of calcium metabolism. It has also been implicated as a potential contributor to the pathophysiology of various extra-skeletal conditions, consisting hypertension, renal disease, and insulin resistance. Objectives: The primary objective of this study was to determine whether oral vitamin D (cholecalciferol) supplementation can lead to improvement of blood pressure in type 2 diabetes patients. Patients and methods: This study was a double blind clinical trial conducted on 60 type 2 diabetes mellitus patients. Exclusion criteria were taking calcium, vitamin D supplements or any drugs effecting calcium and vitamin D metabolism in the past 6 months. Patients were administered weekly vitamin D supplementation (50000 units) for 12 weeks. Serum 25-Hydroxy vitamin D [25(OH)D] level was measured with ELISA method. Results: Five patients (8.3%) had vitamin D deficiency, 27 (45%) had insufficient levels of vitamin D and in 28 (45%) patients vitamin D level was within normal limits. The means of systolic blood pressure (BP) and diastolic BP in patients before intervention were 121 and 80.5 mmHg; after intervention they were 110 and 76.3 mmHg, respectively. After intervention, systolic and diastolic blood pressure levels were significantly less than control group (p< 0.01). Conclusions: In this study we found that weekly vitamin D supplementation (cholecalciferol; 50,000 units for 12 weeks) had beneficial effect on the level of blood pressure in type 2 diabetic patients. Thus, oral vitamin D may help in improvement of hypertension in these patients.
The effects of policosanol (50–500 mg/kg) administered orally for 24 months to Sprague Dawley rats of both sexes were investigated. No differences related to daily clinical observations, weight gain, food consumption, or mortality (survival analysis) between groups were found. Histopathological study showed that the frequency of the occurrence of non-neoplastic and neoplastic (benign and malignant) lesions was similar in the control and policosanol-treated groups. The lesions observed in this study were similar to the spontaneous lesions reported in this species in previous studies. Since no drug-related increase in the occurrence of malignant or benign neoplasms was found, nor acceleration in tumors growth in any specific group was observed, this study shows no evidence of policosanol induced carcinogenicity in this strain of rats. © 1994 Wiley-Liss, Inc.